Design, Synthesis And Biological Activity Study Of Novel Indole Compound

This paper takes indole-3-carboxylic acid as a lead compound and introduces active structures such as acyl hydrazones and bis（amides）.A total of 38 novel indole compounds containing acyl hydrazone structures and 22 novel indole compounds containing bis（amides）structures were designed and synthesized,respectively.The antifungal activities of target compounds A1-A22 were tested against Fo,Mo,and Ss using the mycelial growth rate method as the assay.The antiviral activities of target compounds Z1-Z38 and A1-A22 were tested against Tobacco mosaic virus（TMV）using the half-leaf necrosis method as the assay.Compounds with antiviral activity were screened out,and the antiviral mechanism of the active compounds was preliminarily explored.The work summary of this paper is as follows:1.Indole-3-carboxylic acid was used as a lead compound,and acyl hydrazone and bis（amide）structures with antiviral activity were introduced as structural units.A total of 38 indole compounds containing acyl hydrazone structures and 22 indole compounds containing bis（amides）structures were designed and synthesized.The structures of target compounds Z1-Z38 and A1-A22 were determined by ¹H NMR,¹³C NMR,and HRMS characterization.2.Compounds A1-A22 were tested for their antibacterial activity against Fo,Mo,and Ss using the mycelial growth rate method at a concentration of 50 mg/L.The test results showed that some compounds had certain antibacterial activity.Compound A1 and A22 had inhibition rates of 43.0%and 42.7%,respectively,against Mo.Compound A3 had an inhibition rate of 40.1%against Fo.3.The antiviral activity of compounds Z1-Z38 and A1-A22 against TMV was tested using the half-leaf necrosis method.The results showed that compounds Z4,Z7,and Z38 had EC₅₀values of 92.70 mg/L,104.9 mg/L,and 77.02 mg/L,respectively,which were better than Ningnanmycin（NNM）.Compounds Z21,Z33,and Z36 had protective EC₅₀values of 68.27 mg/L,52.45 mg/L,and 49.88 mg/L,respectively,which were all better than NNM.The inactivation EC₅₀value of compound Z28 was48.62 mg/L,which was also better than NNM.In addition,the therapeutic EC₅₀value of compound A5 was 139.0 mg/L,which was comparable to NNM.4.Z4,Z7,Z28,Z38,and A5 were tested as ligand molecules for molecular docking and molecular dynamics simulations.The results showed that these compounds had strong affinity and stable binding with TMV CP.Compounds Z28 and Z38,which had good passivation activity,were selected for microscale thermophoresis（MST）testing,and the results confirmed the stable binding of these compounds with TMV CP.